The cocaine abuse problem is growing rapidly. Conventional out-patient treatments are not always affective for cocaine abuse. A pharmacological treatment which would reduce cocaine craving would be a useful adjunct to standard treatment. There is evidence from several open clinical trials to suggest that the tricyclic antidepressant desipramine may be such a pharmacological adjunct. We propose to test the efficacy of desipramine in reducing cocaine abuse in a methadone maintenance out-patient population. After obtaining informed consent, 100 methadone patients meeting the DSM-III criteria for cocaine abuse will be randomly-assigned to either methadone, desipramine, and standard counselling or methadone, placebo, and standard counselling in a double-blind manner. The study will take place over 12 weeks. We expect to have 35 patients in each group complete treatment. Compliance will be assured by having patients take the desipramine or placebo at the pharmacy window along with their daily methadone dose. Severity of cocaine abuse and psychiatric diagnosis will be assessed at intake. Patients will be assessed at weekly intervals and 1 and 3 month follow-up points for cocaine craving, cocaine use, and degree of depression. Treatment outcome measures in the areas of employment, medical, family, overall drug and alcohol, legal, and psychological status will be assessed monthly and at follow-up intervals by the ASI. The study will also provide data regarding the correlation, if any, between severity of cocaine abuse, depression or psychiatric diagnosis, and desipramine responsiveness. Results of this study would have immediate relevance in out-patient methadone programs.